Creatine in 2026: a reassuring kidney review and an unsettling mouse study

Creatine monohydrate has spent two decades as the supplement industry's safest claim: cheap, heavily studied, reliably effective. Two papers published eleven days apart in July 2026 pull in opposite directions on that reputation, and neither is easy to dismiss.

The kidney question, answered carefully

On 27 July, a systematic review and meta-analysis in International Urology and Nephrology pooled 26 randomised trials covering 1,036 participants, searched from inception to March 2025, to assess creatine's effect on kidney health in healthy people and in patients with chronic kidney disease [s1].

Creatine supplementation was associated with a significant increase in serum creatinine — mean difference 0.14 mg/dL (95% CI 0.05–0.22, p = 0.002) — with very high heterogeneity (I² = 93.9%) [s1]. Glomerular filtration rate estimated by creatinine-based equations fell by 10.75 mL/min (95% CI −17.48 to −4.02, p = 0.002, I² = 0%) [s1].

Taken alone, those two numbers look alarming. The third undoes them. When filtration was measured directly using Cr-EDTA rather than inferred from serum creatinine, there was no significant difference (mean difference 5.89 mL/min, 95% CI −0.30 to 12.08, p = 0.06, I² = 6.3%) [s1]. Serum urea, albuminuria, proteinuria and urinary creatinine showed no significant differences either [s1]. In the haemodialysis subgroup, serum creatinine rose while serum urea fell [s1].

The authors' conclusion is that the pattern likely reflects altered creatinine metabolism rather than kidney injury, given the absence of change when filtration is measured by Cr-EDTA [s1]. That is a specific and clinically useful finding: it means a routine creatinine-based kidney panel can misread a creatine user, not that the kidney is being damaged. The high heterogeneity in the serum creatinine estimate is a real limit on precision.

The finding nobody expected

On 15 July, Nature Communications published a study reporting that exogenous creatine supplementation promotes tumour metastasis through platelet activation [s2]. The proposed mechanism runs through megakaryocytes, the bone-marrow cells that produce platelets: creatine supplementation raised megakaryocyte creatine levels and upregulated creatine kinase B, and unbiased phosphoproteomics identified a downstream non-canonical STAT5B phosphorylation that switched on platelet functional genes, producing hyperactive, metastasis-promoting platelets [s2].

The causal evidence is genetic and pharmacological. Megakaryocyte-specific knockout of the creatine transporter Slc6a8 or of Stat5b, and pharmacological inhibition of STAT5, each abolished the creatine-driven platelet hyperactivity and prevented the resulting metastasis in mice [s2]. That is a well-constructed mechanistic chain.

What it is not is evidence that creatine causes cancer in people. The metastasis findings are in mouse models [s2]. The human component reported is that supplementation in healthy volunteers produced hyperactive peripheral platelets, which the authors interpret as increasing metastasis risk [s2] — a biomarker change, not a clinical outcome. No human cancer incidence or progression data are reported. Mouse tumour models are notoriously poor predictors of human oncology outcomes, and platelet reactivity is an intermediate measure whose relationship to metastasis in humans is inferred rather than demonstrated here. This is a single paper, in one laboratory's hands, that has not been replicated.

It is also the first serious mechanistic challenge to creatine's safety profile in years, and it concerns a population — people who take it daily and indefinitely — for whom long-term outcome data has never existed.

Meanwhile, the efficacy picture narrowed

The other thing that changed recently is how confident the field can be about how much creatine actually adds.

A randomised trial published in March 2025 tested the assumption directly. Sixty-three participants (34 women, 29 men, aged 31 ± 8) took 5 g/day of creatine monohydrate for 13 weeks — a seven-day wash-in followed by 12 weeks of resistance training — or served as controls [s3]. After the wash-in alone, the supplement group had gained 0.51 ± 1.79 kg more lean body mass than controls (p = 0.03), an effect concentrated in women (0.59 ± 1.61 kg, p = 0.04) [s3]. Then both groups trained, both gained about 2 kg of lean body mass (p < 0.0001), and there was no between-group difference (p = 0.71), in women (p = 0.10) or in men (p = 0.35) [s3]. The authors' reading is that the early gain reflects creatine's short-term effect on body water confounding lean mass measurement, and that a maintenance dose above 5 g/day may be needed to augment growth [s3]. A design note matters here: the control group received no creatine and no placebo, so participants and outcomes were not blinded [s3].

Pooled analyses still favour creatine, with less drama. A dose-response meta-analysis of 61 trials published in September 2025 found creatine increased fat-free mass by 1.39 kg (95% CI 1.07–1.70, p < 0.001) and body mass by 0.89 kg (95% CI 0.76–1.01, p < 0.001), with no significant effect on fat mass, BMI or body fat percentage [s4]. Experienced lifters gained more fat-free mass than novices — 1.82 kg against 1.23 kg — but the difference was not statistically significant [s4].

A meta-analysis of 39 trials in men aged 18 to 30, published in April 2026, found significant gains in fat-free mass (+3.39 kg) and lean body mass (+2.70 kg) when creatine was combined with resistance training but not without it, alongside improvements in Wingate peak power (+71.27 W) and mean power (+39.69 W) in both training contexts [s5]. Its countermovement jump estimate (+2.87 cm) carried heterogeneity of I² = 88.5%, which the authors flag as requiring caution [s5]. Those body composition point estimates are more than double the 61-trial pooled figures [s4], which is a reason to treat them as unstable rather than as an upgrade.

The clearest new signal is in a population the supplement industry markets to less. A meta-analysis of seven randomised trials in 608 postmenopausal women, median duration 38 weeks and mean age around 62, found lean mass favoured creatine by 0.37 kg (95% CI +0.05 to +0.69, I² = 25%), with a 95% prediction interval of −0.10 to +0.84, and leg-press one-repetition maximum improved by 7.5 kg (95% CI +2.2 to +12.8, I² = 0%) [s6]. Benefits appeared when at least 5 g/day was combined with resistance training; trials using 3 g/day or less without training showed no measurable effect [s6]. Bone density was unchanged, adverse events were mild and comparable to placebo, and renal indices were unchanged [s6]. Risk of bias was rated "some concerns" for most included trials, with one large preregistered double-blind trial at low risk [s6].

What to watch

Three specific things. Whether any group replicates the megakaryocyte–platelet finding, particularly with a human outcome rather than a biomarker [s2]. Whether clinical guidance formally recognises that creatinine-based kidney estimates are unreliable in creatine users, since the direct-measurement data now supports that distinction [s1]. And whether trials test maintenance doses above 5 g/day against a proper placebo, which is the question the 2025 randomised trial left open [s3].

Sources

1. [s1] de Souza Almeida A, da Silva LOD, Takahasi BNA, et al. Impact of creatine supplementation on kidney health: a systematic review and meta-analysis. International Urology and Nephrology, 27 July 2026. https://doi.org/10.1007/s11255-026-05287-x
2. [s2] Xie S, Chen R, Sun X, et al. Exogenous creatine supplementation promotes tumor metastasis via megakaryocyte creatine kinase B-STAT5B signaling. Nature Communications, 15 July 2026. https://doi.org/10.1038/s41467-026-74639-z
3. [s3] Desai I, Pandit A, Smith-Ryan AE, et al. The Effect of Creatine Supplementation on Lean Body Mass with and Without Resistance Training. Nutrients, 19 March 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC11944689/
4. [s4] Ashtary-Larky D, Mohammadi S, Hajizadeh L, et al. Creatine supplementation and resistance training: a comparison between novice and experienced lifters. Journal of the International Society of Sports Nutrition, September 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC12777911/
5. [s5] Gu J, Li Y, Xiao J, Zhang Y. Creatine supplementation in young men under resistance versus non-resistance training. Frontiers in Nutrition, 8 April 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC13099317/
6. [s6] Naddafha S, Antonio J, Kreider RB, Stout JR. Creatine monohydrate for lean mass, strength, and bone density in postmenopausal women. Journal of the International Society of Sports Nutrition, 16 May 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC13182165/